Investigator:
Hisashi Umemori, MD, PhD
Name of Institution:
Boston Children’s Hospital/Harvard Medical School, Boston, MA
Project Title:
The nigrostriatal-specific dopaminergic synapse organizer and Parkinson’s disease
Investigator Bio:
Hisashi Umemori is a neuroscientist at Boston Children’s Hospital/Harvard Medical School. The goal of his research is to identify the molecules and mechanisms underlying the establishment of appropriate synaptic circuits in the brain and provide clues for the treatment of disorders associated with impaired synaptic circuits, including Parkinson’s disease (PD). Dr. Umemori’s initial training was as an MD at the University of Tokyo, but early in his clinical career, he decided to devote himself to understanding the basis of the neuropsychiatric diseases that he was unable to treat properly. At the University of Tokyo, he completed his PhD work in which he analyzed the molecular mechanisms underlying myelination and synaptic plasticity. These studies kindled his interest in how synapses form in the brain. As a postdoctoral fellow in Dr. Joshua Sanes’ lab at Washington University in St. Louis, MO, and Harvard University, Dr. Umemori started studying synapse development. He joined the faculty of the University of Michigan in 2006 and moved to Boston Children’s Hospital/Harvard Medical School in 2013. Dr. Umemori’s lab has identified various molecules and mechanisms that regulate the establishment of specific synaptic circuits and their activity-dependent refinement in the brain.
Objective:
To investigate the mechanisms by which only the dopaminergic neurons of the substantia nigra are targeted in PD in order to design specific strategies to effectively treat PD
Background:
There are two distinct dopamine (DA) neuron populations in the midbrain, those in the substantia nigra (SN) that regulate motor behaviors and those in the ventral tegmental area (VTA) that regulate motivation. Unlike the DA neurons in the SN, the DA neurons in the ventral tegmental area (VTA) show a much lower degree of impairment in PD. If we can understand the mechanisms by which only SN DA neurons are targeted in PD, we could design specific strategies to effectively treat PD.
Methods/Design:
We have searched for molecules that regulate the development and function of SN and VTA DA neurons and identified two distinct signaling molecules that are critical for SN and VTA neurons respectively, to establish DA connections. In this project, we will identify the specific functions of these molecules in SN DA neurons and their relationship with PD pathophysiology. We will also investigate whether the activity of these molecules is altered in other PD animal models and explore possible treatment strategies. This work will have a significant impact on the understanding of the pathophysiology of PD and may allow us to design possible treatments for PD.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Why only SN DA neurons, and not VTA DA neurons, are affected in PD is not known. The discovery of key molecules that regulate this differential susceptibility of DA neurons holds excellent potential for the discovery of novel drug targets and the development of promising neuroprotective treatment strategies for PD.